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The Myriad Case:
The Gene Patent Fight Continues
Technology Transfer Tactics
Webinar
October 4, 2012
Kevin E. Noonan, Ph.D.
Patentable Subject Matter
 Under 35 U.S.C. 101: whoever invents or
discovers any new and useful process, machine,
manufacture, or composition of matter, or any new
and useful improvement thereof, may obtain a
patent therefor…
 The Exception: “laws of nature, natural
phenomenon, and abstract ideas are not
patentable subject matter”
 Broad, subjective language that has resisted efforts to
provide clear guidelines
 Creates uncertainty in prosecution and litigation
AMP v. USPTO (“Myriad”)
Myriad: The claims
 Two broad types of claims at issue: claims to
isolated DNA molecules, and diagnostic
method claims
 DNA claims recite “isolated” DNA encoding
specific amino acid sequences (cDNA)
 Also claims to oligonucleotide probes
 Method claims: methods of detecting mutation
or providing a diagnosis/risk assessment
 Method claims involve “comparing” mutant
sequence to normal sequence
4
Myriad: The claims
 Composition of matter claims covering
“isolated DNA” covering the BRCA 1 and
BRCA 2 genes. Claim 1 of US Patent
5,747,282 is representative of this class of
claims:
An isolated DNA coding for a BRCA1
polypeptide, said polypeptide having the amino
acid sequence set forth in SEQ ID NO:2.
5
Myriad: The claims
 Methods of detecting mutations in the BRCA
genes. Claim 1 of US Patent 5,709,999 is the
only claim in this class:
A method for detecting a germline alteration in a
BRCA1 gene, said alteration selected from the group
consisting of the alterations set forth in Tables 12A, 14,
18 or 19 in a human which comprises analyzing a
sequence of a BRCA1 gene or BRCA1 RNA from a
human sample or analyzing a sequence of BRCA1
cDNA made from mRNA from said human sample with
the proviso that said germline alteration is not a
deletion of 4 nucleotides corresponding to base
numbers 4184-4187 of SEQ ID NO:1
6
Isolated DNA claims
 “Isolated DNA”
comes in two
forms: genomic
DNA and cDNA
 Significant
differences in
structure and
how isolated/
prepared
Is DNA a “product of nature”?
 Genomic DNA may
be
 But chemically
modified from
native state
 cDNA certainly is not
 Claims limited to
specific sequence
that does not exist
prior to human
intervention
District Court Decision
 Judge Sweet agrees that DNA an
unpatentable “product of nature”
 DNA is “the physical embodiment of genetic
information”
 Distinguishes other types of “natural
products” (antibiotics, vitamins) on this basis
 Method claim invalid under Bilski
9
Gene Patenting Myths
 The Ownership Myth
 Michael Crichton, ACLU
and “Who Owns You”
 The Information Myth
 “Physical Embodiment of Genetic Information”
 Information is not what’s patented
 “DNA is a chemical compound, albeit a complex one”
Gene Patenting Myths
 The “Inhibits Research” Myth
 No evidence of research inhibition
 >9,000 science articles on BRCA genes
 Progress promoted by disclosure
 The “Natural Product” Myth
 Natural products not patent-ineligible
per se
 Isolated DNA not found in nature
 cDNA not found in nature
Gene Patenting Myths
 The “Didn’t Invent” Myth
 Ignores reality – plants as drug sources
 Antibiotics, antibodies, etc.
 The “Diagnostics” Myth
 Identifying mutation the first step
 Infrastructure costly to develop
 Research scientists vs. diagnostics
laboratories
Gene Patenting Myths
 Gene patents inhibit/prevent
personalized medicine
 Genetic diagnostic methods (generally)
do not infringe isolated DNA claims
 Unnecessary to isolate a gene to detect
a mutation
 Diagnostic methods amenable to other
forms of IP protection (e.g., trade
secret) that are never disclosed (and
hence can never be generic)
A Clash of Cultures
 And traditional one: doctors vs. lawyers
 Another way to think about it: consumers vs.
producers
 Ironically, many of the inventors are doctors
and scientists, and many of the owners are
universities
 Issues beyond patent law: access to medical
care, First Amendment issues (access to
medical information), ethics and morality
Federal Circuit I Decision
 Federal Circuit reversed in 2011:
 Patent-ineligibility: diagnostic method claims –
comparing/analyzing DNA sequences are
abstract mental steps
 Patent-eligibility: screening method claims –
screening therapeutics by measuring growth
rates in transformed cells (which are not natural
products)
 Method similar to the one the high court deemed unpatentable in Prometheus, except that it involves a
cell that does not occur in nature.
 Patent-eligibility: composition of matter claims
to oligonucleotides, genomic DNA and cDNA
Federal Circuit I Decision (cont.)
 Method claims: claims reciting merely
“analyzing” or “comparing” fail the
“machine-or-transformation” test
 Claims to a screening method does not,
since cell growth in presence of putative
BRCA inhibitor is transformative
Federal Circuit I: Majority
 Judge Lourie: “isolated DNA” patenteligible because it satisfies the Supreme
Court “test” from Funk Brothers and
Chakrabarty that a natural product can be
patented provided that:
 there is “a change in the claimed
composition's identity compared with what
exists in nature” and
 “that human intervention has given ‘markedly
different,’ or ‘distinctive,’ characteristics.”
 Chemical changes in isolated DNA enough
Federal Circuit I: Concurrence
 Judge Moore: DNA a polymer, like
nylon
 Isolated DNA not just purified from
nature
 Also reads precedent as requiring
alteration of natural product
 This rationale convincing for cDNA and
oligonucleotide fragments because do
not occur in nature – made by man
Federal Circuit I: Concurrence
 “Isolated DNA” claims are a “closer
case”
 Not entirely convinced that isolation
effects sufficient change to satisfy
precedent
 But, not “drawing on a blank canvas” cannot ignore 30 years of PTO practice
and CAFC precedent (Amgen v. Chugai
etc.)
 Change in the law up to Congress
“Isolation” vs. “Purification”
 Both the majority opinion and Judge
Moore’s concurring opinion set up a
dichotomy
 “Isolated” DNA as claimed patenteligible because it has been chemically
transformed
 Thus, DNA has not “merely” been
isolated
 Implications for other biological
molecule-based inventions
Federal Circuit I: Dissent
 Judge Bryson: “common sense”
conclusion that human DNA not patenteligible (including oligonucleotide primers)
 Applies the same Supreme Court
precedent, comes to the opposite
conclusion
 Concern seems to be negative effects on
whole genome sequencing
 Discounts PTO practice and deference to
Congress, citing DOJ position
DOJ amicus brief
 On the one hand, the brief argues that
manipulated DNA (cDNA, vectors,
oligonucleotides, etc.) are patent-eligible
because they show “the hand of man”
 On the other, isolated genomic DNA not patenteligible because it is not sufficiently changed
 Tries to “split the baby” by arguing on both
sides of the issue
 Genetic diagnostic methods also patentineligible, since merely a “natural phenomena”
 Not from the Department of Commerce or the
PTO and seemingly with little or no PTO input
Myriad: DOJ brief
 Unfortunately, this does little to satisfy either
constituency
 Worse, if this logic is accepted by the court the
effects go far beyond DNA
 All biologic molecules, and many classical
“products of nature” (antibiotics, antibodies,
vitamins, hormones, enzymes, etc.) are
essentially just “isolated,” often less changed
than is isolated DNA
 Also, the goal of biologic drugs is to make the
drug as similar to the “natural product” as
possible
Myriad Cert. Petition I
 Questions Presented:
1. Are human genes patentable?
2. Did the court of appeals err in adopting a new
and inflexible rule, contrary to normal standing
rules and this Court's decision in Medimmune,
Inc. v. Genentech, Inc. . . . that petitioners who
have been indisputably deterred by Myriad’s
“active enforcement” of its patent rights
nonetheless lack standing to challenge those
patents absent evidence that they have been
personally and directly threatened with an
infringement action?
Supreme Court GVR
 Supreme Court granted certiorari,
vacated the Federal Circuit’s decision,
and remanded for reconsideration in
view of Mayo v. Prometheus
 Federal Circuit directed parties (and
amici) to address “gene” claims and
claim 20 (screening method claim) but
not diagnostic claims
Prometheus v. Mayo:
Supreme Court Decision re: §101
• Patent claimed a method for optimizing treatment of an
immune-mediated gastrointestinal disorder with 6thioguanine
• Recited steps of administering the drug to a patient and
detecting 6-thioguanine or 6-methyl-mercaptopurine
(metabolite) in blood
• Recited inferring step of therapeutic efficacy when 6thioguanine levels in red blood cells are between 230
pmol and 400 pmol per 8 x 108 red blood cells
• Levels outside these ranges “indicates a need” to adjust
administration amounts accordingly – but does not recite
affirmative steps of adjusting
Prometheus in the Federal Circuit
• Steps for administering a drug and determining
metabolites can be transformative and satisfy Bilski
• Such steps can be “method of treatment” steps that are
“always transformative”
• Involving “natural processes” not determinative, since
“every transformation of physical matter . . . occurs as
the result of natural processes”
• A process for chemical or physical transformation of a
physical object or substance are “virtually self-evidently”
patent-eligible subject matter
• Inclusion of a mental step does not negate patenteligibility
Question Before U.S. Supreme Court
“This case concerns whether a patentee can
monopolize basic, natural biological relationships.
…
The question presented is: Whether 35 U.S.C. §
101 is satisfied by a patent claim that covers
observed correlations between blood test results
and patient health, so that the claim effectively
preempts all uses of the naturally occurring
correlations, simply because well-known methods
used to administer prescription drugs and test
blood may involve ‘transformations’ of body
chemistry.”
Decision: not patentable
• Court considers these claims to recite a law of
nature
“Beyond picking out the relevant audience, namely
those who administer doses of thiopurine drugs,
the claim simply tells doctors to: (1) measure
(somehow) the current level of the relevant
metabolite, (2) use particular (unpatentable) laws
of nature (which the claim sets forth) to calculate
the current toxicity/inefficacy limits, and (3)
reconsider the drug dosage in light of the law.”
“Routine, Conventional”
• Basis: besides the law of nature, the claims
merely recite “routine” or “conventional” steps
“[T]he steps in the claimed processes (apart from the
natural laws themselves) involve well-understood,
routine, conventional activity previously engaged in
by researchers in the field”
“And since they are steps that must be taken in order
to apply the laws in question, the effect is simply to
tell doctors to apply the law somehow when treating
their patients.
“Not Enough” Added
• Patent-eligibility requires something “more
than” simply reciting a law of nature
“To put the matter more succinctly, the claims inform a
relevant audience about certain laws of nature; any
additional steps consist of well understood, routine,
conventional activity already engaged in by the scientific
community; and those steps, when viewed as a whole,
add nothing significant beyond the sum of their parts
taken separately.”
Natural Law not patentable
• “Administration” step not relevant to patenteligibility
“While it takes a human action (the administration of a
thiopurine drug) to trigger a manifestation of this
relation in a particular person, the relation itself
exists in principle apart from any human action. The
relation is a consequence of the ways in which
thiopurine compounds are metabolized by the
body—entirely natural processes. And so a patent
that simply describes that relation sets forth a
natural law.”
Negative Consequences
•The claims “tie up the doctor’s subsequent treatment
decisions”
•The claims “threaten to inhibit the development of
more refined treatment recommendations (like that
embodied in Mayo’s test), that combine Prometheus’
correlations with later discovered features of
metabolites, human physiology or individual patient
characteristics.”
•”[U]pholding the patents would risk disproportionately
tying up the use of the underlying natural laws,
inhibiting their use in the making of further
discoveries"
Fed. Cir. Decision – Part II
 Substantially reiterated its previous
decision in August 2012: claims to isolated
human DNA satisfy the requirements of 35
U.S.C. 101.
 The Prometheus decision did not change
the standards for assessing patent
eligibility for compositions of matter
previously set forth.
Fed. Cir. Decision – Part II (cont.)
 Prometheus does not control the
question of patent eligibility of
Myriad's isolated DNA claims
because they involve compositions of
matter, rather than method claims.
 The majority: the claimed isolated
DNA molecules are "not found in
nature" and are "man-made, a
product of human ingenuity.”
Fed. Cir. Decision – Part II (cont.)
 Important distinction: characterizes the
district court opinion as setting forth a
“categorical rule” of patent-ineligibility,
contrary to Bilski and Chakrabarty
 Specifically addresses the Supreme
Court’s concern (in Mayo) regarding preemption, because compositions of matter
are narrower in scope than claims to
natural laws
Federal Circuit II: Dissent
 Judge Bryson maintained his “common
sense” objection to patenting human DNA
not patent-eligible (including
oligonucleotide primers)
 Now adheres to plaintiffs’ arguments that
such claims “pre-empt” scientific efforts
 While finding Mayo ”instructive” also
opines that it did not overturn Funk Bros.
or Chakrabarty
Myriad Cert. Petition II Filed
 Questions Presented:
1. Are human genes patentable?
2. Did the court of appeals err in upholding a method claim by
Myriad that is irreconcilable with this Court's ruling in Mayo
Collaborative Services v. Prometheus Labs, Inc.?
3. Did the court of appeals err in adopting a new and inflexible
rule, contrary to normal standing rules and this Court's
decision in Medimmune, Inc. v. Genentech, Inc. . . . that
petitioners who have been indisputably deterred by Myriad’s
“active enforcement” of its patent rights nonetheless lack
standing to challenge those patents absent evidence that
they have been personally and directly threatened with an
infringement action?
Some Hypotheticals to Ponder
 Are/should these be patentable:
 Isolated chemical compound from crude oil
useful as a lubricant
 Isolated antibiotic produced by bacteria
 Isolated chemical compound from a plant
useful as a drug
 Isolated protein from an animal useful to
cure/ameliorate human disease
 Isolated cucumber gene that extends
freshness
 Isolated Human gene (erythropoietin)
Consequences and Recommendations
Consequences of CAFC decision
 For now, “gene patents” claim patenteligible subject matter
 Practically, consensus decision on gene
patent-eligibility for cDNA covers most
patents on genes
 Isolated genomic DNA claims less certain,
but less valuable
 Oligonucleotide claims more certain as
man-made manufactures
Consequences of CAFC decision
 Diagnostic method claims less certain
 Claims at issue flawed by claim language
 Interpreted to broadly encompass mere
comparison of germline and patient BRCA
gene sequences by inspection
 Claims do not recite affirmative steps for
obtaining sequence
 Myriad has many other claims that do
recite such steps
Practical Implications From
Myriad (and Prometheus)
 Neither decision as sweeping as it first looks
 Some diagnostic method claims are alive and
well, provided they are claimed properly
 Gene patent claims are alive and well, however
there is a risk that the Supreme Court could
rule broadly and negatively for “naturally
occurring” DNA (as opposed to cDNA)
 The key is to have “enough” more in the claims
than simply “stating a natural law and then the
words ‘apply it’”.
Some Claim-drafting
Strategies
• Avoid claims that only produce
information
• Include active steps directing more than
mental activity
• Make sure the “law of nature” does not
constitute the only novel feature of the
claim
Claim-drafting Strategies
• General principles:
- the more specific, the better
- draft claims with active steps
- consider “method of treatment”
clams or steps when possible
- remember who the infringer will be
- include “unconventional limitations”
Recommendations: Isolated DNA
claims
 If “isolated” is insufficient, many DNA
claims invalid
 Consequences depend on what the claims
are protecting
 For making therapeutic proteins, recombinant
cell claims should survive
 Vector claims should also be patentable
(man-made)
 Kit claims should also be patentable, as
manufactures
46
Recommendations: Patented
technology
 “Narrowing” reissue a possibility
 For DNA claims, can limit to
“manufactured” DNA – claim scope
expressly outside chromosomal DNA by
structure
 Can also narrow vector claims to these
embodiments
 Diagnostic method claims to include
“active” steps like sequencing
47
Recommendations: Patented
technology
 In litigation, DNA claims not usefully
asserted
 But then, what damage (usually) from
DNA claim alone?
 Recombinant cells should survive Myriad
even at Supreme Court
 Pharmaceutical infringement should
involve at least use of recombinant cells
48
Claim-drafting Strategies: Prometheus
A method of administering 6-thiopurine to a
patient in need thereof for treating an
immune-mediated gastrointestinal disorder,
comprising the step of administering a
therapeutically effective amount of the drug
that produces no less than 230 pmol and no
more than 400 pmol per 8x108 red blood cells
in blood from the patient.
Claim-drafting Strategies: Myriad
A method for diagnosing a predisposition for
breast cancer in a patient comprising the
steps of: a) obtaining a biological sample
from the patient; b) determining a sequence
for BRCA1 or BRCA2 from the sample; c)
detecting a breast cancer-related mutation in
either BRCA1 or BRCA2 from the patient;
and d) treating a patient having a breast
cancer-related mutation with [effective drug
such as taxol].
Natural Products Thought
Experiment
Researchers discover a molecule produced in
humans that regulates blood pressure
completely. It can replace all existing blood
pressure medications and can be used in
surgery, etc. to stabilize blood pressure.
Remembering that the method of making
something doesn’t itself render a molecule
patent-eligible, is a perfect replica of this blood
pressure regulator patent-eligible (regardless of
how it is made)?
Thank you!
Kevin E. Noonan, Ph.D.
Partner [ ] 300 South Wacker Drive [ ] Chicago, Illinois 60606-6709
312-913-2145 direct [ ] 312-913-0001 main [ ] 312-913-0002 fax
[email protected] [ ] www.mbhb.com [ ] www.patentdocs.org